Endocytosis: The Nanoparticle and Submicron Nanocompounds Gateway into the Cell

Manzanares, Darío; Ceña, Valentı́n

doi:10.3390/pharmaceutics12040371

Cited by 296 publications

(228 citation statements)

References 111 publications

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“…Additionally, gemini cationic lipids (GCL) have demonstrated to be efficient gene nanovectors [ 34 , 35 , 36 ], especially when an imidazolium group was included in their structure [ 37 , 38 ]. Both synthetic strategies are focused on overcoming the biological barriers that the nanocarrier encounters once it enters the bloodstream [ 39 ], as well as on improving the endocytosis pathway [ 40 ]. In this regard, the inclusion of a co-adjuvant lipid in the formulation is a common approach for enhancing the fusogenic properties of the complex formed by lipids and nucleic acids (lipoplex) with the cell membrane.…”

Section: Introductionmentioning

confidence: 99%

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

et al. 2020

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A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presented.

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Section: Introductionmentioning

confidence: 99%

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

et al. 2020

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“…To do so, we selected a simple liposomal composition based on the neutral (zwitterionic) phospholipid phosphatidylcholine. Vesicular size, surface charge and modifications, as well as lipid composition, are widely known to affect the liposome internalization rate and mechanism, with a consequent effect on intracellular dispatch [20][21][22][23][24]. However, it is the interplay of these features that determines the biological outcome.…”

Section: Discussionmentioning

confidence: 99%

Following the Fate of Dye-Containing Liposomes In Vitro

Cauzzo

Nystad

Holsæter

et al. 2020

IJMS

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The rather limited success of translation from basic research to clinical application has been highlighted as a major issue in the nanomedicine field. To identify the factors influencing the applicability of nanosystems as drug carriers and potential nanomedicine, we focused on following their fate through fluorescence-based assays, namely flow cytometry and imaging. These methods are often used to follow the nanocarrier internalization and targeting; however, the validity of the obtained results strictly depends on how much the nanosystem’s fate can be inferred from the fate of fluorescent dyes. To evaluate the parameters that affect the physicochemical and biological stability of the labeled nanosystems, we studied the versatility of two lipid dyes, TopFluor®-PC and Cy5-DSPE, in conventional liposomes utilizing well-defined in vitro assays. Our results suggest that the dye can affect the major characteristics of the system, such as vesicle size and zeta-potential. However, a nanocarrier can also affect the dye properties. Medium, temperature, time, fluorophore localization and its concentration, as well as their interplay, affect the outcome of tracing experiments. Therefore, an in-depth characterization of the labeled nanosystem should be fundamental to understand the conditions that validate the results within the screening process in optimization of nanocarrier.

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“…While at 24 h both nanoparticles promote similar peptide uptake by DC, at two hours, the β-cyclodextrin derivative AMC6 nanoparticle was much more efficient. This difference indicates the possible relevance of the uptake pathway for the rate of cargo delivery into the cell [ 35 ]. So, it would be reasonable to assume that the presence of mannose in the G4-70/30 PAMAM dendrimer structure would promote its uptake via specific mannose receptors (MMR, DC-SIGN) coupled to clathrin-mediated endocytosis while polycationic amphiphilic cyclodextrins can be taken up by both clathrin-dependent and clathrin-independent mechanisms being the later more relevant in the case of plasmid DNA transfection [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

et al. 2020

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Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

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Endocytosis: The Nanoparticle and Submicron Nanocompounds Gateway into the Cell

Cited by 296 publications

References 111 publications

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

Following the Fate of Dye-Containing Liposomes In Vitro

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

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